Differential DNA cross-linking and cytotoxicity in PHA-stimulated human lymphocytes exposed to melphalan, m-L-sarcolysin and peptichemio.

DNA interstrand, as well as DNA protein cross-linking, was more efficient in phytohaemagglutinin-stimulated human lymphocytes exposed to m-L-sarcolysin as compared to melphalan at equivalent concentrations of the drug. The cellular uptake of m-L-sarcolysin was more efficient as compared to melphalan. With peptichemio, a mixture of 6 peptides containing m-L-sarcolysin, an intermediate level of DNA cross-linking was found. The differences in DNA cross-linking between the 3 drugs were parallel to differences in cytotoxicity. Peptichemio has been ascribed anti-metabolic properties in addition to the alkylating properties conferred by its m-L-sarcolysin content. In the phytohaemagglutinin-stimulated lymphocytes, however, the effect of peptichemio seems linked to its capacity for DNA cross-linking.